Due to ever-increasing antibiotic resistance, structurally novel antibacterials with a new mode of action have become increasingly important in the treatment of bacterial infections. Effective antibacterials should exhibit potent activity against a number of human and veterinary pathogens, including gram-positive aerobic bacteria such as multiply-resistant staphylococci and streptococci, anaerobic organisms such as bacteroides and clostridia species, and acid-fast organisms such as Mycobacterium tuberculosis and Mycobacterium avium. The present invention provides structurally novel pharmaceutical compounds with expanded spectrum of antibacterial activity, including the activity against aerobic gram-negative organisms.
Among newer antibacterial agents, oxazolidinone compounds are the most recent synthetic class of antimicrobials active against a number of pathogenic microorganisms. However, oxazolidinones generally do not demonstrate useful levels of activity against aerobic gram-negative organisms. Thus, the use of these oxazolidinone antibacterial agents is limited to infectious states caused by gram-positive bacteria. We have now discovered that [3.1.0] bicyclic oxazolidinone derivatives of oxazolidinones of the present invention possess enhanced anti-gram-positive activity and/or expand the spectrum of antimicrobial activity to include gram-negative organisms such as Haemophilus influenza and Moraxella catarrhalis. 